Use of DisBa-01, a recombinant disintegrin from Bothrops alternatus, to study the role of alphavbeta3 integrin on the beta-estradiol in vitro effects in breast tumor cells

• Grant number: 16/07043-5
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): June 01, 2016
• Effective date (End): May 31, 2017
• Field of knowledge: Biological Sciences - Morphology - Cytology and Cell Biology
• Principal Investigator: Heloisa Sobreiro Selistre de Araújo
• Grantee: Tayná Oliveira Costa Santos
• Host Institution: Centro de Ciências Biológicas e da Saúde (CCBS). Universidade Federal de São Carlos (UFSCAR). São Carlos , SP, Brazil
• Associated research grant: 13/00798-2 - The extracellular matrix in aging, exercise and in the tumor microenvironment, AP.TEM

Abstract

Breast Cancer is one of the cancers that affects more women worldwide. Among the risk factors associated with this disease, it is possible to mention the exposure to endogenous estrogens and hormonal therapy. In cellular studies estradiol was featured with carcinogenic potential, capable of boosting the cancer malignancy, making it more aggressive. The incidence of breast cancer increases progressively with age, and the use of Hormone Replacement Therapy for menopause (HRT) is associated with increased risk of developing the cancer. These facts highlight the need to develop alternative therapies for HRT and more effective anti-tumor treatments. Surveys show the existence of a cross-talk between integrins, cell adhesion receptors and signaling by estradiol, two factors involved in tumor progression, demonstrating the importance of the study of this relationship. The disintegrins are small peptides able to interact with integrins present on the cell surface and inhibit its function. The disintegrin DisBa-01 recombinantly produced from the venom of the species Bothrops alternatus, is capable of inhibiting integrin ±v²3 and displays anti-metastatic and anti-angiogenic properties, thus an important research target for combating tumors. The objective of this project is to explore the DisBa-01 as a possible antagonist to the effects of estradiol in human breast adenocarcinoma cells dependent on estrogen (MCF-7) using methods to determine the integrin profile and the cell cycle in stimulated cells, and for protein characterization of estrogen-receptor signaling and integrin ±v²3. (AU)